ADAR1 forms a complex with dicer to promote MicroRNA processing and RNA-induced gene silencing

Hiromitsu Ota, Masayuki Sakurai, Ravi Gupta, Louis Valente, Bjorn Erik Wulff, Kentaro Ariyoshi, Hisashi Iizasa, Ramana V. Davuluri, Kazuko Nishikura*

*Corresponding author for this work

Research output: Contribution to journalArticle

165 Scopus citations

Abstract

Adenosine deaminases acting on RNA (ADARs) are involved in RNA editing that converts adenosine residues to inosine specifically in double-stranded RNAs. In this study, we investigated the interaction of the RNA editing mechanism with the RNA interference (RNAi) machinery and found that ADAR1 forms a complex with Dicer through direct protein-protein interaction. Most importantly, ADAR1 increases the maximum rate (Vmax) of pre-microRNA (miRNA) cleavage by Dicer and facilitates loading of miRNA onto RNA-induced silencing complexes, identifying a new role of ADAR1 in miRNA processing and RNAi mechanisms. ADAR1 differentiates its functions in RNA editing and RNAi by the formation of either ADAR1/ADAR1 homodimer or Dicer/ADAR1 heterodimer complexes, respectively. As expected, the expression of miRNAs is globally inhibited in ADAR1-/- mouse embryos, which, in turn, alters the expression of their target genes and might contribute to their embryonic lethal phenotype.

Original languageEnglish (US)
Pages (from-to)575-589
Number of pages15
JournalCell
Volume153
Issue number3
DOIs
StatePublished - Apr 25 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Ota, H., Sakurai, M., Gupta, R., Valente, L., Wulff, B. E., Ariyoshi, K., Iizasa, H., Davuluri, R. V., & Nishikura, K. (2013). ADAR1 forms a complex with dicer to promote MicroRNA processing and RNA-induced gene silencing. Cell, 153(3), 575-589. https://doi.org/10.1016/j.cell.2013.03.024